21829-25-4

Pharmacological effects

Nifedipine is a kind of dihydropyridine calcium antagonists, it can inhibit the Ca2 + uptake of cardiac and vascular smooth muscles, and it can expand the coronary artery , increase coronary blood flow,and improve myocardial ischemic tolerance, at the same time, it can expand peripheral arteries and reduce peripheral vascular resistance,and relieve coronary artery spasm, and increase coronary blood flow, improve myocardial ischemia,in order to decrease the blood pressure. Small doses do not affect blood pressure, when expanding coronary artery ,it is a better anti-angina drug .It is used for the prevention and treatment of angina pectoris,with no adverse effects on respiratory function, its efficacy is best particularly for angina pectoris coronary spasm and obstructive airway disease with angina , its efficacy is superior to β-blockers.It is also applied to all types of high blood pressure, including severe and resistant hypertension. Treatment of refractory congestive heart failure may be taking this long. It is also used for the treatment of primary pulmonary hypertension, diffuse esophageal spasm and bronchial asthma, duodenal ulcers, urinary tract obstruction, exercise-induced asthma, achalasia. Nifedipine has a certain selectivity on vascular smooth muscles , the direct negative inotropic effect and denaturation effect on the heart are weak, systemic administration of it does not cause the heart rate slowing down ,on the contrary, the heart rate performances reflected increase. The above information is edited by the lookchem of Tian Ye.

Production methods

O-nitrobenzaldehyde, methyl acetoacetate, methanol, ammonia are refluxed together , then froze , crystallize,after filtration, nifedipine crude is obtained . The crude product is recrystallized through methanol .then the product is derived , yield rate is 50%.

Toxicity grading

Highly toxic

Acute toxicity

Oral-rat LD50: 1022 mg/kg; Oral-Mouse LD50: 310 mg/kg.

Flammability and hazard characteristics

Combustion produces toxic fumes of nitrogen oxides; medicinal side effects: low blood pressure, cardiac disease, local blood flow disease, high blood sugar, psychosis.

Storage Characteristics

Ventilated , low-temperature, drying; and it is kept separately from food raw materials warehouse.

Extinguishing agent

Dry powder, foam, sand, carbon dioxide, water spray.

Manufacturing Process

45 grams 2-nitrobenzaldehyde, 80 cc acetoacetic acid methyl ester, 75 cc methanol and 32 cc ammonia are heated under reflux for several hours, filtered off, cooled and, after suction-filtration, 75 grams of yellow crystals of MP 172° to 174°C are obtained, according to US Patent 3,485,847.

Therapeutic Function

Coronary vasodilator

World Health Organization (WHO)

Nifedipine is a dihydropyridine calcium channel blocker. It is listed in the WHO Model List of Essential Drugs. The 10mg tablet is retained on the list for short-term treatment of hypertension. Sustained-release preparations are advised for long-term treatment.

Air & Water Reactions

Aqueous solutions are very sensitive to light. . Insoluble in water.

Reactivity Profile

Nifedipine is sensitive to light.

Fire Hazard

Flash point data for Nifedipine are not available; however, Nifedipine is probably combustible.

Biological Activity

L-type calcium channel blocker.

Biochem/physiol Actions

Nifedipine is a L-type Ca2+ channel blocker; and induces apoptosis in human glioblastoma cells. Nifedipine has neuroprotection activity and protects substantia nigra. Nifedipine has antioxidant potential. Nifedipine downregulates inflammatory cytokines like macrophage inflammatory protein-2 (MIP-2), tumor necrosis factor-α (TNF-α). Nifedipine has antihypertensive properties. Nifedipine inhibits extracellular region of adenosine A2a receptor (ADORA2A) gene.

Mechanism of action

Nifedipin causes relaxation of smooth musculature, dilation of coronary and peripheral arteries, and reduction of peripheral resistance and arterial blood pressure, and enhances oxygen supply to the heart.

Synthesis

Nifedipine, dimethyl ether 1,4-dihydro-2,6-dimethyl-4-(2′-nitrophenyl)-3,5- piridindicarboxylic acid (19.3.16), is synthesized by a Hantsch synthesis from two molecules of a β-dicarbonyl compound—methyl acetoacetate, using as the aldehyde component— 2-nitrobenzaldehyde and ammonia. The sequence of the intermediate stages of synthesis has not been completely established.

Drug interactions

Potentially hazardous interactions with other drugs Aminophylline: possibly increases aminophylline concentration. Anaesthetics: enhanced hypotensive effect. Anti-arrhythmics: concentration of dronedarone increased. Antibacterials: metabolism accelerated by rifampicin; metabolism possibly inhibited by clarithromycin, erythromycin and telithromycin. Antidepressants: metabolism possibly inhibited by fluoxetine; concentration reduced by St John’s wort; enhanced hypotensive effect with MAOIs. Antiepileptics: effect reduced by carbamazepine, barbiturates, phenytoin and primidone. Antifungals: metabolism possibly inhibited by itraconazole and ketoconazole; concentration increased by micafungin; negative inotropic effect possibly increased with itraconazole. Antihypertensives: enhanced hypotensive effect, increased risk of first dose hypotensive effect of post-synaptic alpha-blockers; occasionally severe hypotension and heart failure with beta-blockers. Antivirals: concentration possibly increased by ritonavir; use telaprevir with caution. Cardiac glycosides: digoxin concentration possibly increased. Ciclosporin: may increase ciclosporin level, but not a problem in practice; nifedipine concentration may be increased. Cytotoxics: metabolism of vincristine possibly reduced. Grapefruit juice: concentration increased - avoid. Magnesium salts: profound hypotension with IV magnesium. Tacrolimus: increased tacro

Metabolism

Nifedipine is metabolised in the gut wall and oxidised in the liver via the cytochrome P450 isoenzyme CYP3A4, to inactive metabolites. Excreted mainly as metabolites via the kidney

Chemical properties

Yellow crystals. Melting point 172-174 ℃. Soluble in acetone, chloroform, ethyl acetate, dissolved in hot methanol, insoluble in water. It easily deteriorates in case of light.

Category

Toxic substances

Brand name

Adalat (Bayer); Afeditab (Watson);Procardia (Pfizer).

General Description

Nifedipine, 1,4-dihydro-2, 6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate dimethyl ester(Adalat, Procardia), is a dihydropyridine derivative thatbears no structural resemblance to the other calcium antagonists.It is not a nitrate, but its nitro group is essential for itsantianginal effect. As a class, the dihydropyridines possessa central pyridine ring that is partially saturated. To this, positions2 and 6 are substituted with an alkyl group that mayplay a role in the agent’s duration of action. In addition, positions3 and 5 are carboxylic groups that must be protectedwith an ester functional group. Depending on the type ofester used at these sites, the agent can be distributed to variousparts of the body. Finally, position 4 requires an aromaticsubstitution possessing an electron-withdrawinggroup (i.e., Cl or NO2) in the ortho and/or meta position.